Silver nanoplate compositions and methods

ABSTRACT

Embodiments of the present invention relate to methods for preparing high optical density solutions of nanoparticle, such as nanoplates, silver nanoplates or silver platelet nanoparticles, and to the solutions and substrates prepared by the methods. The process can include the addition of stabilizing agents (e.g., chemical or biological agents bound or otherwise linked to the nanoparticle surface) that stabilize the nanoparticle before, during, and/or after concentration, thereby allowing for the production of a stable, high optical density solution of silver nanoplates. The process can also include increasing the concentration of silver nanoplates within the solution, and thus increasing the solution optical density.

INCORPORATION BY REFERENCE TO ANY PRIORITY APPLICATIONS

This application is a continuation of U.S. application Ser. No.14/681,379, filed Apr. 8, 2015, which is a continuation of InternationalApplication No. PCT/US2013/063920, filed Oct. 8, 2013 and published inEnglish as WO 2014/058904 on Apr. 17, 2014, which claims the benefit ofpriority from U.S. Provisional Application 61/795,149, filed on Oct. 11,2012, each of which is incorporated by reference in its entirety,herein. Any and all applications for which a foreign or domesticpriority claim is identified in the Application Data Sheet as filed withthe present application are hereby incorporated by reference under 37CFR 1.57.

PARTIES TO JOINT RESEARCH AGREEMENT

The invention described herein was created subject to a Joint ResearchAgreement between Sienna Labs, Inc. and nanoComposix, Inc.

BACKGROUND

Field of the Invention

The invention relates to a method for preparing high optical densitysolutions of silver platelet nanoparticles (e.g., nanoplates) and tonanoparticles, solutions and substrates prepared by said methods.

Description of the Related Art

Nanoparticles, including nanospheres, nanorods, nanowires, nanocubes,nanoplates, as well as other shapes can be synthesized from a range ofmaterials. In one embodiment, a platelet nanoparticle is a nanoplate.Nanoparticles made from metals including gold and silver have uniqueoptical properties which can be tuned to interact with light throughoutthe electromagnetic spectrum due to the localized surface plasmonresonance supported by these nanomaterials. Technologies that takeadvantage of the unique optical properties of silver nanoparticlesinclude, but are not limited to, diagnostic, photonic, medical, andobscurant technologies. A subset of these technologies includingphotothermal tumor ablation, hair removal, acne treatment, woundhealing, and antimicrobial applications among others, may use solutionsof nanoparticles with high optical densities. Silver nanoplates, whichare also known as silver platelet nanoparticles or nanoprisms, are ofparticular interest for technologies that utilize nanoparticle opticalproperties due to their tunable spectral peaks and extremely highoptical efficiencies. While methods of fabricating silver nanoplates viaphotoconversion (Jin et al. 2001; Jin et al. 2003), pH-controlledphotoconversion (Xue 2007), thermal growth (Hao et al. 2004; Hao 2002;He 2008; Metraux 2005), templated growth (Hao et al. 2004; Hao 2002),and seed mediated growth (Aherne 2008; Chen; Carroll 2003; Chen; Carroll2002, 2004; Chen et al. 2002; He 2008; Le Guevel 2009; Xiong et al.2007) have been developed, these methods generate relatively dilutesolutions with correspondingly low visible and near-infrared opticaldensity.

SUMMARY

For many silver nanoplate applications, a more concentrated solution ofthe silver nanoplates is of utility and can be particularlyadvantageous. In some instances, when as-fabricated solutions of silvernanoplates are concentrated to yield a higher particle density underpreviously developed methods, the shape of the nanoparticle can undergoa change resulting in a shift in optical properties, such as opticaldensity. In many cases, these changes result in an undesirabledegradation of the nanoparticle's optical properties. Accordingly,several embodiments of the present invention provide methods ofpreparing silver nanoplates solutions in higher concentrations withincreased optical density while reducing degradation of the silvernanoplates' optical properties. In various embodiments, methods of thepresent invention provide for preparing high optical density solutionsof silver nanoplates from dilute silver nanoplate solutions thatpartially, substantially, or fully preserve the shape and opticalproperties of the fabricated silver nanoplates when the particleconcentration is increased.

Various embodiments of the invention provide methods for preparing highoptical density solutions of silver nanoplates, as well as thenanoparticles and solutions prepared by those methods. In oneembodiment, the process comprises the replacement of one or moreoriginal components (e.g., chemical or biological agents) bound to, orotherwise coupled to, the nanoparticle surface with a stabilizing agent.In another embodiment, the stabilizing agent does not replace theoriginal component but rather supplements or alters the originalcomponent. The stabilizing agent can be a biological or chemical agentthat stabilizes the nanoplates before, during, and/or afterconcentration, thereby allowing for the production of a stable, highoptical density solution of silver nanoplates. In one embodiment, theprocess also comprises a method of increasing the concentration ofsilver nanoplates within the solution, and thus increasing the solutionoptical density. In several embodiments, the stability (e.g., thecharacteristics of the nanoparticles in the solution, such as shape,size, optical properties, peak response, plasmonic properties, etc.) ofthe high optical density solution is unaffected or substantiallyunaffected during the process. Several embodiments of the inventioncomprise a high optical density solution of silver nanoplates that havebeen stabilized with stabilizing agents (e.g., surface bound molecules,chemical agents, and/or biological agents). In one embodiment, theinvention comprises a solution of silver nanoplates that have beensurface functionalized with chemical or biological agents that arephysisorbed to the surface, molecularly bound to the surface throughspecific interactions, or encapsulate each nanoparticle.

In one embodiment, a high optical density solution of silver nanoplatesis associated with a substrate. In one embodiment, a portion of thenanoplates in solution bind to the substrate to create ananoplate-substrate composite. The high optical density solutions ofsilver nanoplates can be exposed to substrates to generate nanoplatecomposites where a substantial portion of the surface area of asubstrate is coated with nanoplates. In some embodiments the substratecomprises fibers, cloth, mesh, bandages, socks, wraps, other articles ofclothing, sponges, high porosity substrates, particles with edge lengthsgreater than 1 micron, beads, hair, skin, paper, absorbent polymers,foam, wood, cork, slides, roughened surfaces, biocompatible substrates,filters, and/or medical implants.

In several embodiments, a process for increasing the optical density ofa stable, silver nanoplate solution, comprises (i) providing a solutioncomprising a plurality of silver nanoplates having a plate shape andhaving a peak optical density between 0.1-10 cm⁻¹; (ii) adding astabilizing agent to the solution; (iii) adding a buffer to thesolution; and (iv) concentrating the buffer-containing solution to forma concentrated solution, wherein the concentrated solution comprises aplurality of silver nanoplates having the plate shape, and wherein theconcentrated solution has a peak optical density greater than 10 cm⁻¹.

In several embodiments, a method for producing a stable, high opticaldensity solution of silver nanoplates comprises the following: (i)adding a stabilizing agent to a solution of silver nanoplates, (ii)adding a buffer (e.g., such as a buffer containing a water soluble salt)to the solution of silver nanoplates, (iii) mixing the stabilizing agentwith the buffer and the silver nanoplates over a period of timesufficient for the stabilizing agent to interact with the water solublesalt in the buffer on the surface of the silver nanoplates, and (iv)concentrating the solution to a peak optical density greater than 10cm⁻¹ (e.g., 50-1500 cm⁻¹).

The stabilizing agents can include one or more of sodium citrate, awater soluble polymer, (such as polystyrene sodium sulfonate and/or ahydrocarbon polymer derivatized with sulfonate), a poly vinyl basedpolymer (such as polyvinyl alcohol (PVA) and/or polyvinylpyrrolidone(PVP)), polyethylene glycol, polyacrylic acid, or dextran. The watersoluble salt can include one or more of the sulfates, carbonates,chromates, borates, phosphates, and sulfites, acetates, and nitrates. Invarious embodiments, the combination of the stabilizing agent and abuffer containing one or more water soluble salts provides stabilizationto the nanoplate formulation, wherein one of the components of the saltcan interact with the stabilizing agent to crosslink the stabilizingagent and increase the stability of a coating on the silver nanoplate.In one embodiment an initial solution of silver nanoplates can beproduced from a solution comprising one or more stabilizing agents and asilver source (e.g., such as a silver salt, silver seeds), and in whichchemical agents, biological agents, mixing, electromagnetic radiation,and/or heat are used to reduce the silver source (e.g., photoconversion,pH controlled photoconversion, thermal growth, templated growth, and/orseed mediated growth).

In various embodiments, a process for concentrating a solution of silvernanoplates includes the steps of providing a solution comprising aplurality of silver nanoplates having a peak optical density below 10cm⁻¹ (e.g., 0.1-9.9 cm⁻¹, 1-9 cm⁻¹, 3-7 cm⁻¹, 1-5 cm⁻¹, and/or 5-10cm⁻¹), adding a stabilizing agent to the solution, adding a buffercontaining a water soluble salt to the solution, and concentrating thesolution to a peak optical density greater than 10 cm⁻¹ (e.g., 80-150cm⁻¹, 900-1100 cm⁻¹, 100 cm⁻¹, 1000 cm⁻¹ or more). In variousembodiments, the peak optical density in increased by 10%, 50%, 100%,200%, 500%, 1,000%, 10,000% or more, and/or increased by a ratio of1:1.5, 1:2, 1:5, 1:10 or more, and/or increased by a factor of 1, 1.5,2, 5, 10, 25, 50, 100, 1000 or more.

In various embodiments, the silver nanoplates have an aspect ratio ofbetween 1.5 and 50 (e.g., 1.5-10, 25-50). In one embodiment, the silvernanoplates comprise an edge length between 10 nm and 300 nm (e.g.,50-250, 65-100 nm). In various embodiments, the stabilizing agentcomprises sodium citrate, or at least one water soluble polymer selectedfrom the group consisting of polystyrene sodium sulfonate and ahydrocarbon polymer derivatized with sulfonate. In some embodiments, thewater soluble salt comprises one or more of sulfates, carbonates,chromates, borates, phosphates, and sulfites, acetates, and nitrates. Inone embodiment, the stabilizing agent comprises at least one of thegroup consisting of polyvinyl pyrollidone, polyvinyl alcohol,polyethylene glycol, polyacrylic acid, and dextran. In one embodiment,the stabilizing agent comprises a thiol-containing molecule. Thethiol-containing molecule can comprise a dihydrolipoic acid or aderivative thereof. The process optionally includes the steps ofisolating the concentrated nanoplates and encapsulating the isolatedconcentrated nanoplates (e.g., with silica or another material). In oneembodiment, the process includes the step of concentrating theencapsulated nanoplates to an optical density greater than 10 cm⁻¹(e.g., 100 cm⁻¹, 1000 cm⁻¹ or more). The stabilizing agent is addedprior to the formation of the silver nanoplates. In one embodiment, thenanoplates are concentrated by tangential flow filtration. In oneembodiment, the silver concentration is greater than 1.0 mg/mL (e.g.,1-1000, 10-300 mg/mL).

In various embodiments, a process for generating metal oxide coatedsilver nanoplates is provided. The method can include the steps ofproviding a solution of silver nanoplates having a peak absorptionspectrum between 500 and 1500 nm (e.g., 600-1400, 800-1200 nm) and anoptical density greater than 10 cm⁻¹ (e.g., 100 cm⁻¹, 1000 cm⁻¹ or more)and contacting this solution with a solution of metal oxide or metaloxide precursor in an amount sufficient to form a metal oxide coating onan exterior surface of the silver nanoplates. In certain embodiments thesilver nanoplates are associated with a stabilizing polymer (e.g.,polyvinyl pyrollidone, polyvinyl alcohol, or a combination thereof)prior to contact with the metal oxide precursor, such as by disposingthe stabilizing polymer on an exterior surface of the silver nanoplates.In various embodiments, the metal oxide is silica or includes silica.

In various embodiments, a process for generating a solution of silvernanoplates includes the steps of providing a solution comprising areducing agent, a stabilizing agent, a water soluble polymer, and asilver salt, forming a plurality of silver seeds from the solution,growing the plurality of silver seeds into a plurality of silvernanoplates in the solution to form a silver nanoplate solution, adding astabilizing agent to the silver nanoplate solution, adding a buffercontaining a water soluble salt to the silver nanoplate solution, andconcentrating the silver nanoplate solution to a peak optical densitygreater than 10 cm⁻¹ (e.g., 100 cm⁻¹, 1000 cm⁻¹ or more).

In various embodiments, a composition comprises or consists essentiallyof a solution of silver nanoplates, wherein the silver nanoplatescomprise a poly vinyl polymer. In some embodiments, the poly vinylpolymer comprises polyvinyl pyrollidone or polyvinyl alcohol. In severalembodiments, the composition (e.g., solution) comprises one or moresalts, such as water soluble salts (e.g., sulfates, carbonates,chromates, borates, phosphates, and sulfites, acetates, and nitrates).

In various embodiments, the poly vinyl polymer is associated with thesalt, the poly vinyl polymer coats at least a portion of the silvernanoplates, and/or the poly vinyl polymer is disposed on an exteriorsurface of the silver nanoplates. In one embodiment, the solutioncomprises silver nanoplates in a concentration effective to adhere to anon-metal coating material present in the solution. The solution may beformulated to be concentrated. In some embodiments, the optical densityof the solution or of the silver nanoplates is greater than 10 cm⁻¹(e.g., 100 cm⁻¹, 1000 cm⁻¹ or more). The solution may contain a salt(sulfates, carbonates, chromates, borates, phosphates, and sulfites,acetates, and nitrates) at a concentration greater than 0.1 mM (e.g.,0.1 mM to 10 mM). In one embodiment, the solution has a pH greater than7 (e.g., 8-13). In some embodiments, an absorption spectrum of thesilver nanoplates comprises a peak wavelength of between 500 and 1500 nm(e.g., 600-1400, 550-1100, 810-830, 1000-1100 nm). In one embodiment,the solution comprises bicarbonate. The silver nanoplates may besilica-coated. The silver nanoplates can have edge lengths between 10 nmand 500 nm (e.g., 50-300, 100-150 nm).

In various embodiments, a composition comprises or consists essentiallyof a solution of silver nanoplates bonded to a shell material comprisinga poly vinyl polymer. In one embodiment, the silver nanoplates aresubstantially coated with the poly vinyl polymer. In variousembodiments, the composition includes a metal oxide, the metal oxidecomprises silica, the poly vinyl polymer comprises polyvinyl alcohol orpolyvinylpyrrolidone, the silver nanoplates are bonded to polyvinylalcohol and silica, and/or the silver nanoplates are bonded topolyvinylpyrrolidone and silica, or any combination thereof. In oneembodiment, the composition includes a moiety selected from an aminemoiety and a mercapto moiety. In one embodiment, the moiety is bound tothe silica. In one embodiment, the composition includes aluminum. In oneembodiment, the optical density of the solution is greater than 10 cm⁻¹(e.g., 100-1100 cm⁻¹, or more). In one embodiment, the optical densityof the silver nanoplates is greater than 10 cm⁻¹ (e.g., 100 cm⁻¹, 1000cm⁻¹, 11-5000 cm⁻¹, or more). In some embodiments, the solutioncomprises a water soluble salt (such as sulfates, carbonates, chromates,borates, phosphates, and sulfites, acetates, and nitrates) at aconcentration greater than 0.1 mM (e.g., 0.5 mM to 2 mM, 0.1 mM to 10mM). In one embodiment, the pH is greater than 7 (e.g., 8, 9, 10, 11,12, 13). In one embodiment, the silver nanoplates comprise a peakwavelength of between 500 and 1500 nm (e.g., 700-1300, 810-830,1000-1100 nm).

In various embodiments, a composition includes silver nanoplates atleast partially coated by a shell material that includes a poly vinylpolymer, wherein the mean thickness of the shell material is between 1nm and 50 nm (e.g., 5, 15, 40 nm). In one embodiment, the silvernanoplates have at least one edge length of between 10 nm and 500 nm.(e.g., 25, 100, 250, 300 nm).

In various embodiments, a kit comprises or consists essentially of oneor more containers comprising nanoplates with an optical density greaterthan 10 cm⁻¹ (e.g., 100 cm⁻¹, 1000 cm⁻¹ or more), a solution suitablefor coating nanoplates with a shell of metal oxide, and instructions foruse thereof. In one embodiment, the nanoplates comprise a poly vinylpolymer. In one embodiment, the poly vinyl polymer interacts (e.g.,cross links or otherwise couples) with the water soluble salt (e.g.,sulfates, carbonates, chromates, borates, phosphates, and sulfites,acetates, and nitrates).

In various embodiments, a solution includes silver nanoplates at leastpartially coated by a silica coating, wherein the silver nanoplatescomprise a peak optical density of greater than 10 cm⁻¹ (e.g., 11-5000cm⁻¹, 90-1100 cm⁻¹, or more). In one embodiment, the silica coating hasa shell thickness between 2 and 100 nm (e.g., 10-70, 30-90, 40-60 nm).In one embodiment, the solution comprises a water soluble salt (e.g.,sulfates, carbonates, chromates, borates, phosphates, and sulfites,acetates, and nitrates) at a concentration greater than 0.1 mM (e.g.,0.1 mM to 10 mM). In one embodiment, the solution has a pH greater than7 (e.g., 9, 12, 13). In one embodiment, the silver nanoplates have apeak absorption spectrum comprising a peak wavelength between 500 nm and1500 nm (e.g., 800-1400 nm). In one embodiment, the silica coating isdisposed on an exterior surface of the silver nanoplates. In oneembodiment, the coating includes an amine moiety or a mercapto moiety.In one embodiment, the coating further includes aluminum. In oneembodiment, the coating includes bicarbonate. In one embodiment, thecoating includes polyvinylpyrrolidone. In one embodiment, the silvernanoplates comprise a thickness between 1 nm and 50 nm (e.g., 10-40,15-25, 5-30). In one embodiment, the silver nanoplates comprise at leastone edge length between 10 nm and 500 nm (e.g., 20-400, 50-250,300-450).

In some embodiments, a process for generating a solution of silvernanoplates with extremely high optical density includes the steps of (i)adding a concentration stabilizing chemical agent to a solution ofsilver nanoplates or precursor reagents and (ii) increasing theconcentration of silver nanoplates to increase the optical density ofthe solution.

In various embodiments, the silver nanoplates have an aspect ratio ofbetween 1.5 and 25 (e.g., 1.5-10, 1.5-5, 10-30, 25-50); and/or thenanoplate has an edge length between about 10 nm and 250 nm (e.g.,25-180, 50-150 nm); and/or the nanoplate is triangular in cross section;and/or the nanoplate is circular in cross section. In one embodiment,the perimeter of the nanoplate cross section has between 4 and 8 edges(e.g., 5, 6, 7). In various embodiments, the solution of silvernanoplates is formed using one or more of a photoconversion method, apH-controlled photoconversion method, a thermal growth method, a seedmediated growth method, and/or a solution comprising a shape stabilizingagent or agents and a silver source. In various embodiments, chemical orbiological agents, and/or electromagnetic radiation, and/or heat, or acombination thereof are used to reduce the silver source. In oneembodiment, the solution of silver nanoplates is formed from somecombination of a reducing agent, a shape stabilizing agent, a lightsource, a heat source, and a silver source.

In one embodiment, an acid, base, or buffer (also termed a “bufferingagent”) is added to change the solution pH. In various embodiments, theconcentration stabilizing chemical agent is added prior to, during,and/or after the formation of the silver nanoplates. In one embodiment,the concentration stabilizing chemical agent acts as a shape stabilizingagent. In one embodiment, the concentration stabilizing chemical agentacts as a reducing agent. In one embodiment, the concentrationstabilizing chemical agent acts as an agent to change the solution pH.

In one embodiment, the concentration stabilizing chemical agent is awater soluble polymer. In various embodiments, the polymer is any one ormore of a derivative of polysulfonate, sodium polystyrene sulfonate, aderivative of a vinyl polymer, and a polyvinyl alcohol (PVA). In variousembodiments, the PVA has a molecular weight of less than about 80,000Dalton, between about 80,000 Dalton and 120,000 Dalton, and/or more thanabout 120,000 Dalton. In one embodiment, the polymer ispolyvinylpyrrolidone (PVP). In various embodiments, the PVP has amolecular weight of less than about 20,000 Dalton, more than about20,000 Dalton, between about 20,000 Dalton and 60,000 Dalton, and/ormore than about 60,000 Dalton. In one embodiment, the polymer is anethylene oxide derivative.

In one embodiment, the polymer is a polyethylene glycol (PEG). Invarious embodiments, the PEG has a molecular weight of less than about5,000 Dalton, between about 5,000 Dalton and 10000 Dalton, and/or morethan about 10000 Dalton. In one embodiment, the PEG contains a singlefunctional group. In one embodiment, the PEG contains two functionalgroups. According to some embodiments, the functional group or groupsconsist of one or more of the following: an amine, thiol, acrylate,alkyne, maleimide, silane, azide, hydroxyl, lipid, disulfide,fluorescent molecule, and/or biotin, or combinations thereof. In oneembodiment, the functional group or groups can be any one or more of anamine, thiol, acrylate, alkyne, maleimide, silane, azide, hydroxyl,lipid, disulfide, fluorescent molecule, and/or biotin. In oneembodiment, the concentration stabilizing agent is a carbohydratederivative. In various embodiments, the polymer is a monosaccharide, adisaccharide, an oligosaccharide, a polysaccharide, and/or dextran. Invarious embodiments, the dextran has a molecular weight that is lessthan about 2000 Dalton (e.g., 500, 1000, 1500 Dalton), between about2000 Dalton and 5000 Dalton (e.g., 3000, 4000 Dalton), and/or more thanabout 5000 Dalton (e.g., 6000, 8000, 10000 Dalton or more).

In various embodiments, the concentration stabilizing chemical agent isany one or more of a phenol, a monomeric phenol, a dimeric phenol, atrimeric phenol, a polyphenol, a tannic acid, is gum Arabic, abiological molecule, a protein, a bovine serum albumin, streptavidin,biotin, a peptide, an oligonucleotide, a naturally occurringoligonucleotide, a synthetic oligonucleotide, a metal or metalloidoxide, and/or a silicon dioxide shell. In one embodiment, a silicondioxide shell has ranges in thickness from about less than 1 nm to about100 nm (e.g., 2-90, 5-25, 30-70). In one embodiment, a combination ofstabilizing agents is used.

In various embodiments, the solvent can be one or more of water, analcohol, ethanol, isopropyl alcohol, t-butanol, a mixture of a water andan alcohol.

In one embodiment, the concentration of silver nanoplates is increasedusing tangential flow filtration. In one embodiment, the tangential flowfiltration is performed using a tangential flow filter membrane. In oneembodiment, the tangential flow membrane is made from a cellulose esteror mix of cellulose esters.

In various embodiments, the tangential flow membrane is made from one ormore of polyetheresulfone and/or polysulfone. In various embodiments,the tangential flow membrane has a molecular weight cut off of less thanabout 10 kD (e.g., 1, 5, 8 kD), of between about 10 kD and 500 kD (e.g.,50, 250, 400 kD), of more than about 500 kD (e.g., 750, 1000, 5000 kD ormore), of less than about 0.05 μm (e.g., 0.01, 0.03 μm), of betweenabout 0.05 μm and 0.5 μm (e.g., 0.1, 0.25, 0.4 μm), and/or of more thanabout 0.5 μm (e.g., 1.0, 2, 5, 10, 100 μm).

In various embodiments, the silver nanoplate solution is concentrated toproduce a solution with an optical density of greater than about 10cm⁻¹, greater than about 50 cm⁻¹, greater than about 75 cm⁻¹, greaterthan about 100 cm⁻¹, and/or greater than about 500 cm⁻¹ (e.g., 100-1000,100-2000 cm⁻¹).

In one embodiment, the solvent of the concentrated solution is exchangedusing tangential flow filtration. In one embodiment, the concentratedsolution is processed to remove residual chemicals using tangential flowfiltration.

In various embodiments, a solution of nanoparticles comprising silvernanoparticles is coated with a polymer with an optical density greaterthan 100 cm⁻¹ (e.g., 200, 500, 700, 1500 cm⁻¹, or more) In oneembodiment, the solution of silver nanoplates is incubated with asubstrate. In one embodiment, the substrate is removed from the solutionof silver nanoplates and dried.

One embodiment of the present invention provides processes for makingsolutions of plasmonic nanoparticles, such as e.g., silver nanoplates,that are suitable for performing thermomodulation of a target tissueregion. Thermomodulation of a target tissue can be achieved when acomposition comprising a plurality of plasmonic nanoparticles isadministered to a subject under conditions such that an effective amountof the plasmonic nanoparticles localize to a domain of the target tissueregion, and exposing the target tissue region to energy delivered from aexcitation surface plasmon resonance source in an amount effective toinduce thermomodulation of the domain of the target tissue region. Invarious embodiments, materials described herein are useful forperforming targeted ablative or non-ablative heating of tissue. Forexample, in one embodiment, provided is a method for performing targetedablative or non-ablative heating of a tissue to treat a mammaliansubject in need thereof, comprising the steps of (i) topicallyadministering to a skin surface of the subject the composition ofplasmonic nanoparticles including silver nanoplates; (ii) providingpenetration means to redistribute the plasmonic particles from the skinsurface to a component of dermal tissue; and (iii) causing irradiationof the skin surface by light.

In several embodiments, the invention comprises compositions that, whenused with appropriate methods of administration and excitation with alight-based energy source, can achieve noninvasive or minimally-invasivetreatment of skin and underlying tissues, or other accessible tissuespaces with the use of nanoparticles. Use of optical density solutionsof plasmonic nanoparticles, such as e.g., silver nanoplates, with shortpulse width laser excitation (e.g. pulse widths from 0.1 ms to 1s) cancreate steep transient heat gradients that selectively target ablativeor non-ablative heat to structures within several cell layers of whereparticles are localized, e.g. pilosebaceous unit for acne treatment andpore size reduction, targeted epidermal and dermal layers for skinresurfacing and small profile scar remodeling, and hair follicle forpermanent hair removal. The treatment can include, but is not limitedto, hair removal, hair growth and regrowth, and skin rejuvenation orresurfacing, acne removal or reduction, wrinkle reduction, porereduction, ablation of cellulite and other dermal lipid depositions,wart and fungus removal, thinning or removal of scars includinghypertrophic scars, atrophic scars, and keloids, abnormal pigmentation(such as port wine stains), tattoo removal, and/or skin inconsistencies(e.g. in texture, color, tone, elasticity, hydration). Other therapeuticor preventative methods include, but are not limited to, treatment ofhyperhidrosis, anhidrosis, Frey's Syndrome (gustatory sweating), Homer'sSyndrome, and Ross Syndrome, actinici keratosis, keratosis follicularis,dermatitis, vitiligo, pityriasis, psoriasis, lichen planus, eczema,alopecia, psoriasis, malignant or non-malignant skin tumors.

BRIEF DESCRIPTION OF THE DRAWINGS

Further objects, features and advantages of the invention(s) will becomeapparent from the following detailed description taken in conjunctionwith the accompanying figures showing illustrative embodiments of theinvention, in which the following is a description of the drawings. Thedrawings are examples, and should not be used to limit the embodiments.Moreover, recitation of embodiments having stated features is notintended to exclude other embodiments having additional features orother embodiments incorporating different combinations of the statedfeatures. Further, features in one embodiment (such as in one figure)may be combined with descriptions (and figures) of other embodiments.

FIG. 1 illustrates the optical spectrum of a silver nanoplate solutionfabricated using a photoconversion method according to one embodiment ofthe present invention. As fabricated, these silver nanoplates, in oneembodiment, have a peak optical density of less than 1 cm⁻¹ (e.g.,approximately 0.8 cm⁻¹)

FIG. 2 illustrates the optical spectrum of a silver nanoplate solutionfabricated using a seeded growth method according to one embodiment ofthe present invention. As fabricated, these silver nanoplates have apeak optical density of less than 3 cm⁻.

FIG. 3A is a transmission electron microscope image of a silvernanoplate solution fabricated using a photoconversion method accordingto one embodiment of the present invention.

FIG. 3B is a transmission electron microscope image of a silvernanoplate solution fabricated using a seeded growth method according toone embodiment of the present invention.

FIG. 4 is the optical spectra of silver nanoplates without the additionof a stabilizing agent and water soluble salt according to oneembodiment of the invention before tangential flow concentration andafter tangential flow concentration.

FIG. 5 is the normalized optical spectra of silver nanoplates withoutthe addition of a stabilizing agent and water soluble salt according toone embodiment of the invention before tangential flow concentration andafter concentration.

FIG. 6 is the optical spectra according to one embodiment of silvernanoplates combined with polyvinyl alcohol and a water soluble saltbefore concentration and after concentration.

FIG. 7 is the normalized optical spectra according to one embodiment ofsilver nanoplates combined with polyvinyl alcohol and a water solublesalt before concentration and after concentration.

FIG. 8 illustrates an optical extinction spectra of high optical densitynanoplate solutions processed using the methods described in variousembodiments of the invention.

FIG. 9 illustrates steps for producing one embodiment of silvernanoplates by fabricating the silver nanoplates, adding stabilizingagents, concentrating the nanoplates and optionally coating thenanoplates with silica.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

Several embodiments of the present invention comprise processes formaking solutions of plasmonic nanoparticle including silver nanoplatesthat are suitable for performing thermomodulation of a target tissueregion. In one embodiment, thermomodulation of a target tissue can beachieved when a composition comprising a plurality of plasmonicnanoparticles is administered to a subject under conditions such that aneffective amount of the plasmonic nanoparticles localize to a domain ofthe target tissue region. The target tissue region is exposed to energydelivered from a excitation surface plasmon resonance source. The energyis delivered in an amount effective to induce thermomodulation of thedomain of the target tissue region.

Optical Density (O.D.), which is used herein as a synonym forabsorbance, is defined to be the logarithmic ratio of the radiationincident on a material to the radiation transmitted through the material(O.D.=−log₁₀(I₁/I₀) where I₁ is the intensity of transmitted light andI₀ is the intensity of the incident light). For solutions, the opticaldensity is a function of the path length through the liquid sample andis expressed in units of cm⁻¹. In some instances, optical density isexpressed without the unit cm⁻¹—such as in instances in which a standardpath length of 1 cm is used. In some traditional methods ofmanufacturing silver nanoplates, the maximum optical density of silvernanoplates in as-synthesized solutions without any additional processingis typically less than 10 cm⁻¹ (e.g., 0.1-9.9 cm⁻¹, 1-9 cm⁻¹, 3-7 cm⁻¹,1-5 cm⁻¹, and/or 5-10 cm⁻¹). However, according to some embodiments ofthe present invention, silver nanoplates can be produced with increasedoptical densities. Generally, optical densities of solutions containingplasmonic particles including silver nanoplates are most effective withan optical density that is higher than 10 cm⁻¹ (e.g., 11-5000 cm⁻¹,15-2000 cm⁻¹, 20-1000 cm⁻¹, 80-150 cm⁻¹, 90-110 cm⁻¹, 900-1100 cm⁻¹, 100cm⁻¹, 1000 cm⁻¹ or more) and formulated into a pharmaceutical orcosmetic carrier and stable for days, months, weeks, or years withoutalterations in particle shape and/or properties. In one embodiment,optical densities of solutions containing plasmonic particles includingsilver nanoplates are higher than 10 cm⁻¹ (e.g., 11-5000 cm⁻¹, 15-2000cm⁻¹, 20-1000 cm⁻¹, 80-150 cm⁻¹, 90-110 cm⁻¹, 900-1100 cm⁻¹, 100 cm⁻¹,1000 cm⁻¹ or more) and formulated into a pharmaceutical or cosmeticcarrier and stable for days, months, weeks, or years without alterationsin particle shape and/or properties. In one embodiment, the carrier andcomposition are suitable for topical administration to the skin of amammalian subject, such that the plasmonic nanoparticles are present inan effective amount for selective thermomodulation of a component of theskin.

In some embodiments, the nanoparticle formulations are formulated forapplication by a sponge applicator, cloth applicator, direct contact viaa hand or gloved hand, spray, aerosol, vacuum suction, high pressure airflow, or high pressure liquid flow, roller, brush, planar surface,semi-planar surface, wax, ultrasound and other sonic forces, mechanicalvibrations, hair shaft manipulation (including pulling, massaging),physical force, thermal manipulation, and/or other treatments. In someembodiments, nanoparticle formulation treatments are performed alone, incombination, sequentially or repeated 1-24 times, or more. In otherembodiments, the plasmonic nanoparticles are capable of selectivelylocalizing to a first component of the skin, where physical massage orpressure, ultrasound, or heat increase the selective localization of thenanoparticles to this first component. Additionally, the nanoparticlesare selectively removable from components of the skin other than thefirst component, such removal can be accomplished with acetone, alcohol,water, air, peeling of the skin, chemical peeling, waxing, or reductionof the plasmonic compound. Further, in some embodiments thenanoparticles have a coat layer to increase solubility of thenanoparticles in the carrier and/or reduce “stickiness” and accumulationin non-target areas. In one embodiment, at least a portion of anexterior surface of the nanoparticle is modified, such as to include alayer of a polymer, polar monomer, non-polar monomer, biologic compound,a metal (e.g., metallic thin film, metallic composite, metal oxide, ormetallic salt), a dielectric, or a semiconductor. In one embodiment, theexterior surface modification is polar, non-polar, charged, ionic,basic, acidic, reactive, hydrophobic, hydrophilic, agonistic, and/orantagonistic. In one embodiment, at least one dimension of at least onenanoparticle within a solution of plasmonic nanoparticles is below50-100 nm (e.g., 1, 5, 10, 25, 40, 60, 75, 90 nm), and the nanoparticlesurface can be coated with a matrix (e.g. silica) of 10-100 nm thicknessor more (e.g., 20, 50, 75, 150, 200, 500 nm) in order to increase thatdimension or particle to 50-100 nm or more (e.g., 75, 80, 110, 140, 200,800 nm). This increased dimension size can increase the delivery of allnanoparticles to a target region (e.g., hair follicle, pore, skin, etc.)and limit delivery to non-target region (e.g. dermis).

In various embodiments, materials described herein are useful forperforming targeted ablative or non-ablative heating of tissue. Forexample, in one embodiment, provided is a method for performing targetedablative or non-ablative heating of a tissue to treat a mammaliansubject in need thereof, comprising the steps of (i) topicallyadministering to a skin surface of the subject the composition ofplasmonic nanoparticles including silver nanoplates; (ii) providingpenetration means to redistribute the plasmonic particles from the skinsurface to a component of dermal tissue; and (iii) causing irradiationof the skin surface by light. In further or additional embodiments,provided is a method wherein the light source comprises excitation ofmercury, xenon, deuterium, or a metal-halide, phosphorescence,incandescence, luminescence, light emitting diode, or sunlight. In stillfurther or additional embodiments, provided is a method wherein thepenetration means comprises high frequency ultrasound, low frequencyultrasound, massage, iontophoresis, high pressure air flow, highpressure liquid flow, vacuum, pre-treatment with fractionatedphotothermolysis or dermabrasion, or a combination thereof. In stillfurther embodiments, provided is a method wherein the irradiationcomprises light having a wavelength of light between about 200 nm andabout 10,000 nm (e.g., 300-9000, 700-1300, 800-1200, 800-1300, 900-1100,550-1100, 810-830, 1000-1100 nm), a fluence of about 1 to about 100joules/cm² (e.g., 5-20, 40-70, 10-90), a pulse width of about 1femptosecond to about 1 second, and a repetition frequency of about 1 Hzto about 1 THz (e.g., 1-10, 10-100, 100-1000, 1000-10000, 10000-100000Hz or more).

An object of one embodiment of the subject matter described herein is toprovide compositions, that when used with appropriate methods ofadministration and excitation with a light-based energy source canachieve noninvasive and minimally-invasive treatment of skin andunderlying tissues, or other accessible tissue spaces with the use ofnanoparticles. Use of optical density solutions of plasmonicnanoparticles, such as e.g., silver nanoplates, with short pulse widthlaser excitation (e.g. pulse widths from 0.1 ms to 1 s) can create steeptransient heat gradients that selectively target ablative ornon-ablative heat to structures within several cell layers of whereparticles are localized, e.g. pilosebaceous unit for acne treatment andpore size reduction, targeted epidermal and dermal layers for skinresurfacing and small profile scar remodeling, and hair follicle forpermanent hair removal. The treatment can include, but is not limitedto, hair removal, hair growth and regrowth, and skin rejuvenation orresurfacing, acne removal or reduction, wrinkle reduction, porereduction, ablation of cellulite and other dermal lipid depositions,wart and fungus removal, thinning or removal of scars includinghypertrophic scars, atrophic scars, and keloids, abnormal pigmentation(such as port wine stains), tattoo removal, and/or skin inconsistencies(e.g. in texture, color, tone, elasticity, hydration). Other therapeuticor preventative methods include, but are not limited to, treatment ofhyperhidrosis, anhidrosis, Frey's Syndrome (gustatory sweating), Homer'sSyndrome, and Ross Syndrome, actinici keratosis, keratosis follicularis,dermatitis, vitiligo, pityriasis, psoriasis, lichen planus, eczema,alopecia, psoriasis, malignant or non-malignant skin tumors.

Silver Nanoplate Physical Description

In one embodiment, nanoplates, such as silver nanoplates, arecharacterized by lengths along the three principle axes wherein: theaxial length of two of the principle axes is at least two times greaterthan the axial length of the shortest principle axis, and the shortestprincipal axial length is less than about 500 nm (e.g., 450. 400, 350,300, 250, 100, 150, 50, 30, 20, 10 nm). The “edge length” of thenanoplate is defined to be the average of the length of the two longerprinciple axes. The “thickness” of the nanoplate is defined to be theshortest principal axis.

The ratio of the edge length to the thickness is referred to as the“aspect ratio”. In various embodiments the average aspect ratio of thesilver nanoplates is greater than 1.5, 2, 3, 4, 5, 7, 10, 20, 30, or 50and any range therein. In one embodiment the average aspect ratio of thesilver nanoplates is between 1.5 and 25, 2 and 25, 1.5 and 50, 2 and 50,3 and 25, and/or 3 and 50.

In various embodiments a nanoplate has edge lengths less than 500 nm,250 nm, 200 nm, 150 nm, 100 nm, 80 nm, 60 nm or 50 nm. In one embodimentthe nanoplate has edge lengths greater than 5 nm, 10 nm, 20 nm, 30 nm,50 nm or 100 nm. In various embodiments the edge length is from 30 nm to100 nm, 20 nm to 150 nm, 10 nm to 200 nm, 10 nm to 300 nm. In variousembodiments, the nanoplate has a thickness that is less than 500 nm, 300nm, 200 nm, 100 nm, 80 nm, 60 nm, 50 nm, 40 nm, 30 nm, 20 nm, and/or 10nm and any range therein. In various embodiments the nanoplate thicknessis from 5 nm to 20 nm, 5 nm to 30 nm, 10 nm to 30 nm, 10 nm to 50 nm, 10nm to 100 nm.

Various embodiments of silver nanoplates have a variety of differentcross sectional shapes including (but not limited to) circular,triangular, or shapes that have any number of discrete edges. Innon-limiting embodiments, the nanoplates can be shaped as circular,ovals, squares, rectangles, rods, stars, tubes, pyramids, prisms,triangles, branches, or comprised of a planar surface. In variousembodiments the nanoplates have less than 20, 15, 10, 8, 6, 5, or 4edges, and/or any number between 20 and 1. In various embodiments, thenanoplates can have between 1 and 20, 15, 10, 8, 6, 5, 4, or 3 edges. Inone embodiment the nanoplates have more than 2, 3, 4, or 5 edges. Insome embodiments the silver nanoplates have sharp corners and in otherembodiments the corners are rounded. In some embodiments of silvernanoplates, there are a variety of different cross sectional shapeswithin the same sample. In other embodiments of silver nanoplatesolutions greater than 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or90% of the number of particles in solution are silver nanoplates withthe other particles having different shapes including but not limited tospherical, cubic, and irregular. In various embodiments, a silvernanoplate solution has a percentage of silver nanoplates, with otherparticles in the solution having different shapes, including but notlimited to spherical, cubic, and/or irregular. In various embodiments, asilver nanoplate solution has 5% to 100%, 10% to 50%, 50% to 100%, 30%to 60%, 60% to 100%, 40% to 70%, 70% to 100%, 50% to 80%, 80% to 100%,60% to 90%, and/or 90% to 100% of the number of particles in solutionare silver nanoplates with the other particles having different shapesincluding but not limited to spherical, cubic, and/or irregular. In someembodiments, methods can enhance the stability of silver nanoplates tofacilitate increased optical density while retaining at least 50%, 60%,70%, 80%, 90%, 95%, 98% or more of the silver nanoplate shape whileundergoing a concentrating process. In some embodiments, methods canenhance the stability of silver nanoplates to facilitate increasedoptical density while changing shape from the nanoplate to another shape(e.g., spherical, cubic, and/or irregular) in less than 50%, 40%, 30%,25%, 20%, 10%, 5%, 3,%, 2%, 1% of the silver nanoplates while undergoinga concentrating process. In various embodiments the nanoplates can haveone, two, or more flat sides. In another embodiment the nanoplates arepyramidal.

Silver nanoplates have distinct advantages over other plasmonicnanoparticle shapes and compositions. For example, silver nanoplateshave advantages over plasmonic nanoparticle shapes and compositionsincluding gold nanoshells and gold nanorods due to potential for lowerproduction costs (less reaction waste and lower material costs).Furthermore, optical density (O.D.) per weight of metal is greater forsliver nanoplates relative to gold nanorods when randomly oriented insolution and irradiated with non-polarized light because the planarsurface of a nanoplate resonates with both polarizations of incidentlight. Additionally, absorbance of silver nanoplates is higher than thatof gold nanoshells for the same weight of metal as a greater fraction oflight is absorbed versus scattered with a nanoplate architecturerelative to a nanoshell. For many applications, these benefits in costand absorbance can only be realized if nanoplates are stabilized at highconcentration and for long periods of time, which is the subject of oneembodiment of the present invention.

Silver Nanoplate Fabrication

Modern nanoparticle synthesis techniques have enabled the development ofmaterials with unique optical properties for a wide range ofapplications including diagnostic, obscurant, and therapeuticapplications. Silver nanoplates, as fabricated by current traditionalmethods including photoconversion, pH controlled photoconversion,thermal growth, and/or seed mediated growth methods typically haveoptical densities ranging from 0.1 to 10 cm⁻¹ (e.g., e.g., 0.1-9.9 cm⁻¹,1-9 cm⁻¹, 3-7 cm⁻¹, 1-5 cm⁻¹, and/or 5-10 cm⁻¹). A number oftechnologies seek higher optical density solutions of silver nanoplates.Several embodiments of the present invention describe a novel andnon-obvious method for concentrating silver nanoplates and generatinghigher optical density silver nanoplate solutions. For example, invarious embodiments, methods can increase the optical density of silvernanoplate solutions to greater than 10 cm⁻¹, 20 cm⁻¹, 30 cm⁻¹, 50 cm⁻¹,80 cm⁻¹, 100 cm⁻¹, 150 cm⁻¹, 200 cm⁻¹, 300 cm⁻¹, 400 cm⁻¹, 500 cm⁻¹, 600cm⁻¹, 700 cm⁻¹, 800 cm⁻¹, 900 cm⁻¹, and/or 1000 cm⁻¹, or more.

Silver nanoplates may be fabricated using photoconversion (Jin et al.2001; Jin et al. 2003), pH controlled photoconversion (Xue 2007),thermal growth (Hao et al. 2004; Hao 2002; He 2008; Metraux 2005),templated growth (Hao et al. 2004; Hao 2002), seed mediated growth(Aherne 2008; Chen; Carroll 2003; Chen; Carroll 2002, 2004; Chen et al.2002; He 2008; Le Guevel 2009; Xiong et al. 2007), all hereinincorporated by reference, or alternative methods. Alternative methodsaccording to various embodiments of the present invention includemethods in which the silver nanoplates are formed from a solutioncomprising one or more stabilizing agents and a silver source, and inwhich chemical agents, biological agents, mixing, electromagneticradiation, and/or heat are used to reduce the silver source.

An optical spectrum of silver nanoplates fabricated using one embodimentof a photoconversion method is shown in FIG. 1. The peak wavelength ofthe optical spectra (100) is at a wavelength of 775 nm with an opticaldensity of 0.74 cm⁻¹. The optical spectra of silver nanoplatesfabricated using one embodiment of a seed mediated growth method isshown in FIG. 2. The peak wavelength of the optical spectra (200) is ata wavelength of 930 nm with an optical density of 2.58 cm⁻¹. Atransmission electron microscope image of silver nanoplates made using aphotoconversion method is shown in FIG. 3A. A transmission electronmicroscope image of silver nanoplates made using a seed mediated growthmethod is shown in FIG. 3B.

In one embodiment, when as-fabricated nanoplates are concentrated usingtangential flow filtration, the shape of many of the nanoplates canshift to nanospheres, reducing the formulation efficacy, as evidenced byan increased peak height at ˜400 nm which is the peak optical resonanceof spherical silver nanoparticles. FIG. 4 shows the optical density ofone embodiment of a solution of the nanoplates in the absence of aconcentration stabilization agent before (400) and after (410)concentration. The optical resonance peak that corresponds to theplasmon resonance of the nanoplates shifts from 815 nm (420) to 745 nm(430) demonstrating that the average edge length of the nanoplates isreduced.

FIG. 5 shows a normalized plot of the nanoplate spectra shown in FIG. 4.For this solution of nanoplates, the intensity of the peak in the 700nm-850 nm range is correlated to the number of nanoplates in solution.The intensity of the peak in the 400 nm range is correlated to thenumber of spheroidal particles in solution. Before concentration theratio of the longer wavelength peak (520) to the shorter wavelength peak(540) is 3. After concentration the ratio of the longer wavelength peak(530) to the shorter wavelength peak (550) is 0.8. This changing ratiodemonstrates that the silver nanoplates are changing shape and that thenumber of nanoplates in solution is reduced.

In one embodiment, a solution of nanoplates can be stabilized. FIG. 6shows the optical density of one embodiment of a solution of nanoplatesthat have been stabilized by polyvinyl alcohol in a solution of borate(e.g., sodium borate, potassium tetraborate, etc.). The peak wavelengthof the nanoplate peak is the same for both the unconcentrated (620) andconcentrated (630) solutions indicating that the edge length of thenanoplates is the same before concentration (600) and afterconcentration (610). FIG. 7 shows the normalized spectrum whichdemonstrates that the spectral shape of the peak does not change beforeconcentration (700) and after concentration (710), thereby indicatingthat in one embodiment, a surface coating is sufficient to prevent theshape of the nanoparticles from shifting. In various embodiments,greater than 10%, greater than 20%, greater than 30% or greater than 50%of the silver nanoplates change shape without a surface protection. Inother embodiments less than 20%, less than 10% or less than 5% of thesilver nanoplates undergo a shape change if the nanoplates are coatedwith a protective surface coating. In one embodiment, a spectrum of ananoplate solution concentrated to have a peak optical density of ˜900cm⁻¹ is shown in FIG. 8.

In one embodiment, the silver nanoplates are formed in a multi-stepprocess. In one embodiment, the steps to concentrating nanoplates areshown in FIG. 9 and comprise of fabricating the silver nanoplates (900),adding stabilizing agents (910), concentrating the nanoplates (920) andoptionally coating the nanoplates with silica (930). In variousembodiments, the steps can be taken in any order. In one embodiment, afirst step forms silver seeds from an aqueous solution comprising areducing agent, a stabilizing agent, a water soluble polymer and asilver salt. The reducing agent, stabilizing agent and water solublepolymer may be mixed prior to the addition of a silver source. Invarious embodiments, the reducing agent used in the silver seedformation step can be formaldehyde, sodium borohydride, anotherborohydride, hydrogen gas, carbon monoxide gas, hydrazine, or reducingsugars, or combinations of these. In various embodiments, the reducingagent may be present at a concentration of at least 0.1 mM, 1 mM, or 3mM. In various embodiments the reducing agent may be present at aconcentration from 0.1 mM to 1 mM, 0.3 mM to 3 mM, 0.5 mM to 2 mM, 0.1mM to 2 mM, 0.1 mM to 10 mM.

In various embodiments, the stabilizing agent may be a salt, a polymer,or a biomolecule. In one embodiment the stabilizing agent is trisodiumcitrate or another citrate derivative.

In one embodiment, the water soluble polymer is a polyanionic polymerincluding, but not limited to, polymers derivatized with sulfonate,derivatives of polystyrene sulfonate such as an inorganic salt ofpolystyrene sulfonate, or a monovalent salt of polystyrene sulfonate. Inone embodiment the water soluble polymer is poly (sodium styrenesulfonate) (PSSS). In one embodiment the PSSS has a molecular weightbetween about 3 kDa and about 1,000 kDa. In various embodiments the PSSShas a molecular weight of from 3 kDa to 10 kDa, 5 kDa to 50 kDa, 10 kDato 100 k Da, 30 kDa to 300 kDa, 50 kDa, to 500 kDa, 100 kDa to 1000 kDa,300 kDa to 100 kDa, 500 kDa, to 1000 kDa.

In various embodiments, the silver salt may be any water soluble silversalt including but not limited to silver acetate, silver perchlorate,silver nitrate, silver trifluoroacetate, or silver triflate.

In one embodiment, a step for the formulation of silver nanoplatesincludes having the seeds grown into silver nanoplates in an aqueoussolution comprising silver seeds, an acidic reducing agent and a silversalt. In one embodiment, the acidic reducing agent is citric acid orascorbic acid. The silver salt for the step where seeds are grown intosilver nanoplates may be any water soluble silver salt including silveracetate, silver perchlorate, silver nitrate, silver trifluoroacetate,silver triflate, or combinations thereof.

In one embodiment, the silver nanoplates are stirred at a shear flowrate between 1 s⁻¹ and 100,000 s⁻¹ (e.g., at least 10, 50, 100, 200,300, 400, 500, 1000, 2000, 5000, 10000, 20000, 50000, 75000, 90000 s⁻¹).In various embodiments the silver nanoplates are stirred at a shear flowrate from between 10 s⁻¹ and 100 s⁻¹, 50 s⁻¹ and 500 s⁻¹, 100 s⁻¹ and300 s⁻¹, 200 s⁻¹ and 500 s⁻¹, 100 s⁻¹ and 400 s⁻¹, 500 s⁻¹ and 1000 s⁻¹,1000 s⁻¹ and 10000 s⁻¹, 2000 s⁻¹ and 5000 s⁻¹, 1000 s⁻¹ and 2000 s⁻¹,5000 s⁻¹ and/or 10000 s⁻¹.

Silver Nanoplate Coating

In one embodiment, silver nanoplates have molecules that are adsorbed orotherwise bound to the particle surface. The molecules on the surfaceare the reactants or reactant by-products of the synthesis. One objectof this invention is to partially or fully exchange the molecules thatare bound to the surface of the silver nanoplates with other moleculesthat more fully protect the particles from changing shape duringconcentration. Another object of the invention is to use a stabilizingagent during fabrication that generates plate shapes and also stabilizesthe plates during subsequent concentration.

In various embodiments, stabilizing agents that may be utilized includechemical or biological agents that are physisorbed (e.g., absorbed bynon-molecular binding forces) to the surface, molecularly bound to thesurface through specific interactions (e.g. thiol or amine), orencapsulate the surface (e.g. a metal oxide or metalloid oxide shell).In one embodiment, specific chemical agents of interest includepolymers. In one embodiment, specific chemical agents of interestinclude polymers such as polysulfonates. In one preferred embodiment thestabilizing polymer is derivatized with sulfonates. In some embodiments,vinyl polymers, carbohydrates, ethylene oxides, phenols, andcarbohydrates may be employed. Specific examples of these polymersinclude polystyrene sodium sulfonate, polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), polysaccharides, phenol, tannic acid, dextran, andpolyethylene glycol (PEG) including PEG molecules which contain one ormore chemical groups (e.g. amine, thiol, acrylate, alkyne, maleimide,silane, azide, hydroxyl, lipid, disulfide, fluorescent molecule, orbiomolecule moieties). Specific molecules of interest include proteins,peptides, oligonucleotides, biotin, alkane thiols, lipoic anddihydrolipoic acid and derivatives of these acids, bovine serum albumin,streptavidin, neutravidin, wheat germ agglutinin, naturally occurringand synthetic oligonucleotides and peptides, including syntheticoligonucleotides which have one or more chemical functionalities (e.g.amine, thiol, dithiol, acrylic phosphoramidite, azide, digoxigenin,alkynes, or biomolecule moieties). Specific encapsulating chemicalagents of interest include metal oxide shells such as SiO₂ and TiO₂.Stabilizing agents may be added prior to the formation of silvernanoplates, during the formation of silver nanoplates, or after theformation of silver nanoplates. An additional chemical agent of interestis gum arabic. In some embodiments, the stabilizing agent also modifiesthe pH of the solution.

Carrier Solutions

In one embodiment of this invention, the silver nanoplates arefabricated in aqueous solutions. In other embodiments, the silvernanoplates are fabricated in other solutions that can include ethanol,isopropanol, or organic solvents such as heptane, toluene, or butanol.

In one embodiment an acid, base or buffering agent is added to changethe solution pH either before, during, or after the addition of astabilant. In one embodiment, a buffer, typically containing a watersoluble salt, is added. In one embodiment, the water soluble saltcomprises borate. In one embodiment, the water soluble salt comprisessodium borate. In one embodiment the nanoplates are suspended in asodium bicarbonate buffer or a sodium borate buffer. In one embodimentthe pH of the solution after addition of the pH modifying agent isgreater than pH 6, pH 7, pH 8, pH 9, or pH 10. In various embodiments,the pH of the solution after addition of the pH modifying agent is frompH 6 to pH 8, pH 6.0 to pH 9, pH 7 to pH 10, pH 7 to pH 11, pH 8 to pH10, pH 8 to pH 11, or pH 7 to pH 12.

In one embodiment, the combination of a nanoplate coating and a watersoluble salt present in a buffer provides stabilization to the nanoplateformulation. In some embodiments, one of the components of the salt caninteract with the nanoplate coating or stabilizing agent to crosslinkthe coating and increase the stability of the coating. In variousembodiments, such crosslinking can include non-covalent bonds (e.g.,ionic bonds, hydrophobic interactions, hydrogen bonds and van der Waalsforces including dispersion attractions, dipole-dipole anddipole-induced dipole interactions) and/or covalent bonds between thenanoplate surface, water soluble salts, and/or coatingmaterials/stabilizing agents. In some embodiments the presence of thewater-soluble salt present in a buffer changes the binding affinity of astabilizing agent or coating material to the nanoplate surface, e.g., bymodifying the zeta potential and/or charges on the surface of thenanoplate. In other embodiments the water-soluble salt present in abuffer changes the binding affinity of a stabilizing agent or coatingmaterial to itself through covalent or non-covalent binding. In someembodiments the presence of the water-soluble salt intermediates bindingof a stabilizing agent to the surface of a particle by becomingphysisorbed to the particle surface in association with the stabilizingagent. In further embodiments the water-soluble salt intermediatesbinding of polymer to itself by associating with units of thestabilizing agent or coating materials and lowering the free energynecessary for the coating materials to order on or around a nanoplatesurface. In one embodiment, the nanoplate coating is a polymer and thecrosslinking produces a viscoelastic gel surrounding all or a portion ofthe nanoplate. In other embodiments the stabilizing agent is mixed witha buffer containing a water-soluble salt, and both the stabilizing agentand a component of the water soluble salt bind to the surface of thenanoplate. In one embodiment, a polyvinyl based polymer such aspolyvinylalcohol or polyvinylpyrrolidone is mixed with a borate saltsuch as sodium borate. Polyvinylalcohol and borate are can be complexedto form gels via hydrogen bonding (Schultz 1969). In one embodiment,FIG. 6 and FIG. 7 show the effect of stabilizing silver nanoplates withpolyvinyl alcohol and sodium borate before concentration to preserve theshape of the nanoparticles.

Surface Stabilization

In various embodiments, stabilizing agents can be solid or liquidformulations that are added to the silver nanoplate solution. Thestabilizing agents have an affinity for the surface of the silvernanoplates and are able to associate with the plate surface at wideranges of relative concentrations. In some embodiments, bound moleculeson the silver nanoplates are displaced by a stabilizing agent.Alternatively, a stabilizing agent, such as a polymer, is covalentlyattached to a silver atom present on the surface of the nanoplate. Thepolymer coating may extend over all or a portion of the exterior surfaceof a silver nanoplate. For example, at least 5%, 10%, 15%, 20%, 25%,50%, 75%, 80%, 90%, 95%, 99%, 99.9% or greater than 99.9% of theexterior surface of a silver nanoplate is coated with one type ofpolymer or a plurality of different polymer types. In one embodiment,the stabilizing agent is added before the formation of the silvernanoplates while in another embodiment, the stabilizing species is addedafter the synthesis of the silver nanoplates. Thus, provided arecompositions containing polymer-coated silver nanoplates, and solutionscontaining these compositions may have an optical density less than orequal to 10 cm⁻. Alternatively, such solutions have polymer-coatedsilver nanoplates and an optical density greater than 10 cm⁻; thesesolutions can be achieved by concentrating or purifying polymer-coatedsilver nanoplates present in a more dilute solution. In some embodimentsthe stabilants are added to the as-fabricated silver nanoplate solution.In other embodiments, the solution of nanoplates is washed, or theresidual reactants are otherwise removed. In some embodiments, thesuspending solution is exchanged one or more times with one or moresolution, e.g., to wash the nanoplates or to alter the pH of thesolution, before the stabilizing agents are added. Also provided arekits containing, in one or more containers, nanoplates in a solutionhaving an optical density greater than 10 cm⁻¹ and a metaloxide-containing solution or a metal oxide precursor-containing suitablefor coating the nanoplates with a shell (or coating) of the metal oxide.Preferably, the containers are provided with instructions for usethereof. In some embodiments the kits contain nanoplates having acoating containing a poly vinyl polymer. In other embodiments the polyvinyl polymer contains borate. Nanoplates having a stabilizer coatingare characterized as provided herein or otherwise known in the art, suchas by particle analyzers or emission detectors such as NMR, Fouriertransform spectroscopy, mass spectrometry, or similar assays.

Once the stabilizing agent is added, the mixture of the stabilant andthe silver nanoplates can undergo a number of different processesincluding heating, boiling, boiling under reflux, rotary evaporation,vacuum, stirring, stirring with magnetic stir bars, stirring withoverhead mixers, stirring with homogenizers, shaking, microfluidization,refrigeration, and freezing.

Washing and Concentrating

In one embodiment, after the stabilization step is complete, the silvernanoplates can be washed to remove residual reactants or to exchange thesolution with another solution. The exchange of solution can beaccomplished using dialysis, centrifugation, filtration, or tangentialflow filtration (also known as cross flow filtration). In variousembodiments, the number of wash volumes exchanged within the sample iszero, 1, 2, 3, 4, 5, 1 and 5, 5 to 10, 10 to 20, or more than 20 washvolumes, inclusive.

Nanoparticle solutions with optical densities greater than 10 cm⁻¹(e.g., 11-5000 cm⁻¹, 15-2000 cm⁻¹, 20-1000 cm⁻¹, 80-150 cm⁻¹, 90-110cm⁻¹, 900-1100 cm⁻¹, 100 cm⁻¹, 1000 cm⁻ or more) can be fabricated usingcentrifugation, evaporation, filtration, dialysis or tangential flowfiltration. One embodiment of this invention utilizes tangential flowfiltration as the process of concentrating the silver nanoplatesolution. The filter membrane utilized may be formed from a variety ofmaterials. In various embodiments, specific filter membrane materials ofinterest can include cellulose esters, polysulfone, andpolyetheresulfone. In various embodiments, the filter membrane utilizedmay have pores with a molecular weight cutoff of less than about 10 kD,between 10 kD to 500 kD, or more than about 500 kD, and/or pore sizes ofless than about 0.05 μm, between 0.05 μm and 0.5 μm, or larger thanabout 0.5 μm. In various embodiments, the filter membrane utilized mayhave pores with a molecular weight cutoff between 10 kD, to 100 kD, 10kD to 500 kD, 20 kD to 500 kD, 20 kD to 250 kD and/or pore sizes between0.02 μm and 0.1 μm, 0.05 μm and 0.2 μm, 0.05 μm and 0.5 μm, 0.10 μm and0.2 μm, 0.1 μm and 0.5 μm. Tangential flow filtration can also beutilized to change the solvent in which the silver nanoplates aredispersed. In various embodiments, specific solvents of interest includewater and alcohols (e.g. t-butanol, ethanol, and isopropyl alcohol), aswell as other polar or non-polar solvents. Additionally, tangential flowfiltration can be utilized to remove residual chemicals. FIG. 8 shows anembodiment of a solution of nanoplates that has been concentrated to apeak optical absorbance of 930 cm⁻¹.

In various embodiments, the silver nanoplate solution concentration isincreased to produce a final solution with optical densities of greaterthan about 5 cm⁻¹, greater than about 10 cm⁻¹, greater than about 50cm⁻¹, greater than about 75 cm⁻¹, greater than about 100 cm⁻¹, greaterthan about 500 cm⁻¹, and/or greater than about 1000 cm⁻¹. In variousembodiments, the silver nanoplate solution concentration is increased toproduce a final solution with optical densities from between 10 cm⁻¹ to100 cm⁻¹, 30 cm⁻¹ to 300 cm⁻¹, 50 cm⁻¹ to 500 cm⁻¹, 100 cm⁻¹ to 1000cm⁻¹, 300 cm⁻¹ to 3000 cm⁻¹, or 500 cm⁻¹ to 5000 cm⁻¹. One embodiment ofthe invention is where the silver nanoplate solution concentration isincreased to above 10⁶, 10⁷, 10⁸, 10⁹, 10¹⁰, 10¹¹, 10¹² or 10¹³particles per milliliter. In various embodiments, the silver nanoplatesolution concentration is increased to be between 10⁶ and 10¹³, 10⁷ and10¹³, 10⁸ and 10¹³, 10⁹ and 10¹³, 10¹⁰ and 10¹³, 10¹¹ and 10¹³, or 10¹²and 10¹³ particles per milliliter. In various embodiments, the silverconcentration is greater than 0.1, 1.0, 2, 4, 5, 7, 8, 9, and/or 10mg/mL. In various embodiments, the silver concentration is between 0.1to 1.0, 0.3 to 3.0, 0.5 to 5.0, 1.0 to 10.0, 3.0 to 30.0, 5.0 to 50.0,10.0 to 200.0, 1.0 to 200.0, 1.0 to 500.0, or 10.0 to 500.0 mg/mL.

Silica Coating and Shelling

In one embodiment, the concentrated silver nanoplates are encapsulatedwith a shell of silica. The coating may extend over all or a portion ofthe exterior surface of a silver nanoplate. For example, at least 5%,10%, 15%, 20%, 25%, 50%, 75%, 80%, 90%, 95%, 99%, 99.9% or greater than99.9% of the exterior surface of a silver nanoplate is coated withsilica. The concentrated plates can be mixed with an alcohol (e.g.ethanol or isopropanol). In one embodiment an aminosilane ormercaptosilane is added to the solution to bind silane molecules to thesurface of the nanoplates. The binding of silane molecules to thesurface of nanoplates is specific to the surface coating on thenanoplates. Some nanoparticle coatings that stabilize the nanoplatesduring processing will not be compatible with the formation of a silicashell. In one embodiment, the surface of the nanoplates is coated with amolecule that has an affinity for silane molecules in solution. In oneembodiment a polyvinyl based polymer such as polyvinylalcohol orpolyvinylpyrrolidone is bound to the surface of the nanoplate before theaddition of silane molecules. In other embodiments, a polyvinyl basedpolymer surface is complexed with water soluble salt present in a buffer(e.g., one or more of the sulfates, carbonates, chromates, borates,phosphates, and sulfites, acetates, and nitrates) before the addition ofsilane molecules. In other embodiments mercaptohexadecanoic acid,mercaptoundecanoic acid, or other thiol containing acids are bound tothe surface of the nanoplates. Once there are initial silanes bound tothe surface of the nanoplate, additional silane can be added to thesolution in the presence of a base to form a silica shell. In oneembodiment, the nanoplates coated with a silica shell can be transferredto water and concentrated using a concentration method such astangential flow filtration. In another embodiment the silica shells aremixed with a solution of aluminum salt such as aluminum chloride, astabilizing polymer such as polyvinylpyrrolidone, or a buffer such asbicarbonate.

It is an object of this invention to fabricate a solution that comprisesa concentrated solution of silver nanoplates coated with a silica shell.In one embodiment, the peak optical density of the solution as measuredin a 1 cm path length cuvette is above 10, 20, 50, 100, 500, or 1000. Invarious embodiments, the peak optical density of the solution asmeasured in a 1 cm path length cuvette is between 10-100, 20-200,30-300, 50-500, 100-1000, 200-1000, 300-1000, 500-1000, and/or 200-2000,and any combinations therein. In another embodiment the silverconcentration is above 0.1 mg/mL, 1 mg/mL or above 10 mg/mL. In severalembodiments the silver concentration is between 0.1 to 1.0, 0.3 to 3.0,0.5 to 5.0, 1.0 to 10.0, 3.0 to 30.0, 5.0 to 50.0, 10.0 to 200.0, 1.0 to200.0, 1.0 to 500.0, and/or 10.0 to 500.0 mg/mL, and any combinationstherein. In one embodiment, the silica shell thickness is between 2 and100 nm, and in another embodiment between 5 and 50 nm. In variousembodiments, the silica shell thickness is between 3 and 20 nm, 5 and 20nm, 10 and 20 nm, 10 and 50 nm, 10 and 100 nm, 1 and 10 nm, 3 and 30 nm,5 and 50 nm, and/or 5 and 200 nm, and any combinations therein. Thesilica shell can be fabricated from a mixture of silanes including butnot limited to aminopropyl triethoxy silane, mercaptopropyl triethoxysilane and tetraethylorthosilicate. The silica shell can containnitrogen or sulfur atoms. The silica shell can contain amine moieties ormercapto moieties. The silica shell can contain aluminum or sodiumatoms.

In another embodiment the solution contains a buffer, that includes awater soluble salt (e.g., one or more of the sulfates, carbonates,chromates, borates, phosphates, and sulfites, acetates, and nitrates) ata concentration greater than 0.1 mM, 1.0 mM or 10.0 mM. In variousembodiments the water soluble salt concentration may be from 0.1 mM to 1mM, 0.3 mM to 3 mM, 0.5 mM to 5 mM, 1 mM to 10 mM, 1 mM to 30 mM, 1 mMto 50 mM, 1 mM to 1000 mM, and any combinations therein. The solutioncan have a peak absorption wavelength between 500 nm and 1500 nm, 500 nmto 1200 nm, 500 nm to 1000 nm, 600 nm to 1200 nm, 700 nm to 1200 nm, 700nm to 1500 nm, 700 nm to 900 nm, and/or 900 to 1100 nm, and anycombinations therein.

Storage

In various embodiments, the concentrated particles are stored attemperatures below −10, 0, 4, 6, 10, or 20 degrees C. In one embodiment,the particles are frozen and dried under vacuum. In one embodiment, theparticles are freeze dried. In one embodiment, the particles aresupercritically dried. In one embodiment, an additional stabilant orother cryoprotectant is added to the solution before the particles areheat dried or freeze dried.

Composites

In one embodiment of the invention, high optical density solutions ofsilver nanoplates are associated with a substrate. In variousembodiments, examples of substrates include fibers, cloth, mesh,bandages, socks, wraps, other articles of clothing, sponges, highporosity substrates, particles with edge lengths greater than 1 micron,beads, hair, skin, paper, absorbent polymers, foam, wood, cork, slides,roughened surfaces, biocompatible substrates, filters, or medicalimplants. In various embodiments, solutions of silver nanoplates at aconcentration of at least 1 mg/mL, 10 mg/mL, and/or 100 mg/mL areincubated with the substrate. In several embodiments the silvernanoplate concentration incubated with the substrate is between 0.1 to1.0, 0.3 to 3.0, 0.5 to 5.0, 1.0 to 10.0, 3.0 to 30.0, 5.0 to 50.0, 10.0to 20.0, 5.0 to 50.0, 3.0 to 50.0, 1.0 to 100.0 mg/mL, 10.0 to 100.0,20.0 to 100.0, 30.0 to 100.0 mg/mL. In another embodiment, the solutionsof silver nanoplates incubated with the substrate are between 10⁶ and10¹³, 10⁷ and 10¹³, 10⁸ and 10¹³, 10⁹ and 10¹³, 10¹⁰ and 10¹³, 10¹¹ and10¹³, 10¹² and 10¹³ or greater than 10¹³ particles per milliliter. Inanother embodiment the silver nanoplates are prepared at an opticaldensity of at least 10, 20, 50, 100, 300, 500, 1000 and/or 2000 cm⁻¹before incubating with the substrate. In various embodiments the silvernanoplates are prepared at an optical density of between 10-100, 20-200,30-300, 50-500, 100-1000, 200-1000, 300-1000, 500-1000, or 200-2000. Inanother embodiment the substrate is chemically treated to increase thebinding of the nanoplates to the substrate. For example, the substratecould be functionalized with a molecule that yielded a positively ornegatively charged surface. In another embodiment, the pH of theincubating solution is selected in order to optimize binding. In anotherembodiment, the silver nanoplates cover at least 5%, 10%, 20%, 30%, 50%or 75% of the substrate. In various embodiments, the silver nanoplatescover between 5% to 10%, 10% to 100%, 10% to 50%, 50% to 100%, 30% to100%, 30% to 70%, 40% to 80%, 50% to 90%, 60% to 100%, 70% to 100%, 80%to 100%, 90% to 100%, 0% to 5%, o % to 10%, 0% to 20%, 0% to 30%, or 0%to 50% of the substrate. In another embodiment, other solvents orchemicals are added to the incubation solution. In another embodiment abiological linker (e.g. antibodies, peptides, DNA) is used to bind thehigh optical density silver nanoplates to the surface of the substrate.In one embodiment, the incubation is for less than 1 minute, 5 minutes,20 minutes, 60 minutes, or 120 minutes. In various embodiments, theincubation is between 0 to 1 minute, 1 minute to 120 minutes, 5 minutesto 120 minutes, 20 minutes to 120 minutes, 60 minutes to 120 minutes, 5minutes to 60 minutes, 10 minutes to 60 minutes, 20 minutes to 60minutes, 0 minutes to 10 minutes, 0 minutes to 20 minutes, or 0 minutesto 5 minutes.

In one embodiment, the substrate is separated from the incubatingsolution and dried. The substrate can be dried using air drying, heatdrying, freeze drying, or supercritical drying. In another embodimentthe dried substrate can be further processed by soaking the substrate inanother material, painting the substrate with another material, orexposing the substrate to another material that is in the vapor phase.

Other embodiments of the invention will be apparent to those skilled inthe art from consideration of the specification and practice of theinvention disclosed herein. It is intended that the specification andexamples be considered as disclosing certain embodiments of theinvention only, with a true scope and spirit of the invention beingindicated by the following claims.

The subject matter described herein may be embodied in other specificforms without departing from the spirit or essential characteristicsthereof. The foregoing embodiments are therefore to be considered in allrespects illustrative rather than limiting. While embodiments aresusceptible to various modifications, and alternative forms, specificexamples thereof have been shown in the drawings and are hereindescribed in detail. It should be understood, however, that theinvention is not to be limited to the particular forms or methodsdisclosed, but to the contrary, the invention is to cover allmodifications, equivalents, and alternatives falling within the spiritand scope of the various embodiments described and the appended claims.Any methods disclosed herein need not be performed in the order recited.

The methods disclosed herein include certain actions taken by apractitioner; however, they can also include any third-party instructionof those actions, either expressly or by implication. For example,actions such as “identifying a target region of skin tissue” include“instructing the identification of a target region of skin tissue.”

The ranges disclosed herein also encompass any and all overlap,sub-ranges, and combinations thereof. Language such as “up to,” “atleast,” “greater than,” “less than,” “between,” and the like includesthe number recited. Numbers preceded by a term such as “about” or“approximately” or “substantially” include the recited numbers. Forexample, “about 3 mm” includes “3 mm.” The terms “approximately”,“about” and/or “substantially” as used herein represent an amount orcharacteristic close to the stated amount or characteristic that stillperforms a desired function or achieves a desired result. For example,the terms “approximately”, “about”, and “substantially” may refer to anamount that is within less than 10% of, within less than 5% of, withinless than 1% of, within less than 0.1% of, and within less than 0.01% ofthe stated amount or characteristic.

EXAMPLES

The description of specific examples below are intended for purposes ofillustration only and are not intended to limit the scope of theinvention disclosed herein.

Example 1 Silver Nanoplates

Silver nanoplates were synthesized using silver seeds prepared throughthe reduction of silver nitrate with sodium borohydride in the presenceof sodium citrate tribasic and poly sodium styrene sulfonate underaqueous conditions. Silver seed preparation: 21.3 mL of an aqueous 2.5mM sodium citrate tribasic solution was allowed to mix under magneticstirring. 1 mL of a 2 g/L poly styrene sodium sulfonate (PSSS) solutionwas then prepared in a separate beaker. 21.3 mL of a 0.5 mM silvernitrate solution was then prepared by dissolving the salt in water. Oncethe above solutions have been prepared, 1.33 mL of a 0.5 mM sodiumborohydride solution was prepared in 4° C. water. The borohydride andPSSS solutions were then added to the beaker containing the citrate andallowed to mix. The silver nitrate solution was then pumped into thecitrate solution using a peristaltic pump at a rate of 100 mL/min. Thisseed solution was then allowed to stir overnight at room temperature.Silver nanoplates were prepared by mixing 1530 mL Milli-Q water with 35mL of a 10 mM ascorbic acid solution. Once the solution was sufficientlymixed, the prepared silver seed was added to the reactor. 353 mL of a 2mM silver nitrate solution was pumped into the reactor at a rate of 100mL/min. The reaction was mixed for two hours. TEM analysis showed thatover 70% of the particles are nanoplates. The optical density of thesolution was 2.8 cm⁻¹.

Example 2 Concentrated Silver Nanoplates

15 L of silver nanoplates with a peak optical density of about 5 cm⁻¹were mixed with 3.5 g of polyvinylalcohol (PVA) and sodium borate,concentrated using tangential flow filtration using a 500 kD polysulfonetangential flow membrane with 3100 cm² of surface area. The solution wasconcentrated for approximately 90 minutes, and the final solution volumewas reduced from 15 L to 0.5 L. The silver nanoplate solution opticaldensity was increase to about 150 cm⁻¹. Thus, according to oneembodiment, a method for increasing a silver nanoplate solution from 5cm⁻¹ to 150 cm⁻¹ (e.g., an increase of roughly 30 times the opticaldensity) comprises the steps of adding PVA and sodium borate to silvernanoplates, and concentrating the solution with tangential flowfiltration.

Example 3 Concentrated Silver Nanoplates

In one example of concentrating silver nanoplates, 1.2 L of silvernanoplates with a peak optical density of about 4 cm⁻¹ were mixed with 4L of anhydrous ethanol and about 49 mL of ammonium hydroxide solution.0.6 mL of a dilute aminopropyltriethoxysilane (APTES) was added to thesolution. After 15 minutes of incubation, 6.5 mL oftetraethylorthosilicate (TEOS) solution was added. After 24 hours 1 L ofthe solution was concentrated using a 500 kD polysulfone tangential flowmembrane with 1050 cm² of surface area. The final solution volume wasdecreased to 150 mL, increasing the silver nanoparticle solution opticaldensity to about 40 cm⁻¹. Thus, according to one embodiment, a methodfor increasing a silver nanoplate solution from 4 cm⁻¹ to 40 cm⁻¹ (e.g.,an increase of roughly 10 times the optical density) comprises the stepsof adding anhydrous ethanol, ammonium hydroxide solution,aminopropyltriethoxysilane (APTES), and tetraethylorthosilicate (TEOS)to the silver nanoplates, and concentrating the solution with tangentialflow filtration.

Example 4 Nanoplates with a Silica Shell

A silica shell was grown on the surface of 800 nm resonant (˜75 nm edgelength) polyvinylpyrrolidone (PVP) capped silver nanoplates. 400 mL of asolution of 800 nm resonant PVP capped silver nanoplates at aconcentration of 2 mg/mL (20 cm⁻¹ O.D.) was added to 2.3 L of reagentgrade ethanol and 190 mL Milli-Q water under constant stirring. 4.3 mLof dilute aminopropyl triethoxysilane (215 uL APTES in 4.085 mLisopropanol) was then added to the solution, followed immediately by theaddition of 44 mL of 30% ammonium hydroxide. After 15 minutes ofincubation, 31 mL of dilute tetraethylorthosilicate (1.55 mL TEOS in29.45 mL isopropanol) was added to the solution. The solution was thenleft to stir overnight. The nanoplates were then centrifuged on an Ultracentrifuge at 17000 RCF for 15 minutes and reconstituted in Milli-Qwater each time and repeated twice. The silica shell thickness was 15nm. The optical density of the concentrated material was 2040 cm⁻¹.

Example 5

A 40 mL solution of 40 O.D. solution of concentrated silver nanoplatesstabilized with polyvinylalcohol and sodium borate was spun at 3000 RCFfor 30 minutes. The supernatant was removed and the pellet wasre-dispersed with bath sonication. The concentrated silver nanoplateshad an optical density greater than 900 O.D. as is shown in FIG. 8.

Example 6 Concentrated Nanoplates on a Substrate

A 5 mL solution of 1000 O.D. silver nanoplates was added to a 3″×3″section of absorbent cloth (Absorber Synthetic Drying Chamois, CleanTools). After addition, the substrate was allowed to air dry. Oncedried, the silver nanoplates were bound to the surface of the absorbentcloth and were not released when the cloth was subsequently wet andwater removed by applying pressure.

REFERENCES

-   Aherne, D. L., D. M.; Gara, M.; Kelly, J. M., 2008: Optical    Properties and Growth Aspects of Silver Nanoprisms Produced by    Highly Reproducible and Rapid Synthesis at Room Temperature.    Advanced Materials, 18, 2005-2016.-   Chen, S., and D. L. Carroll, 2003: Controlling 2-dimensional growth    of silver nanoplates. Self-Assembled Nanostructured Materials    Symposium (Mater. Res. Soc. Symposium Proceedings Vol. 775),    343-348|xiii+394.-   Chen, S. H., and D. L. Carroll, 2002: Synthesis and characterization    of truncated triangular silver nanoplates. Nano Letters, 2,    1003-1007.-   Chen, S., and D. L. Carroll, 2004: Silver nanoplates: Size control    in two dimensions and formation mechanisms. Journal of Physical    Chemistry B, 108, 5500-5506.-   Chen, S. H., Z. Y. Fan, and D. L. Carroll, 2002: Silver nanodisks:    Synthesis, characterization, and self-assembly. Journal of Physical    Chemistry B, 106, 10777-10781.-   Hao, E., G. C. Schatz, and J. T. Hupp, 2004: Synthesis and optical    properties of anisotropic metal nanoparticles. Journal of    Fluorescence, 14, 331-341.-   Hao, E. K., K. L.; Hupp, J. T.; Schatz, G. C., 2002: Synthesis of    Silver Nanodisks using Polystyrene Mesospheres as Templates. J Am    Chem Soc, 124, 15182-15183.-   He, X. Z., X.; Chen, Y.; Feng, J., 2008: The evidence for synthesis    of truncated silver nanoplates in the presence of CTAB. Materials    Characterization, 59, 380-384.-   Jin, R., Y. Cao, C. A. Mirkin, K. L. Kelly, G. C. Schatz, and J. G.    Zheng, 2001: Photoinduced Conversion of Silver Nanospheres to    Nanoprisms. Science, 294, 1901-1903.-   Jin, R., Y. C. Cao, E. Hao, G. S. Metraux, G. C. Schatz, and C. A.    Mirkin, 2003: Controlling anisotropic nanoparticle growth through    plasmon excitation. Nature, 425, 487.-   Le Guevel, X. W., F. Y.; Stranik, O.; Nooney, R.; Gubala, V.;    McDonagh, C.; MacCraith, B. D., 2009: Synthesis, Stabilization, and    Functionalization of Silver Nanoplates for Biosensor Applications. J    Phys Chem C, 113, 16380-16386.-   Metraux, G. S. M., C. A; 2005: Rapid Thermal Synthesis of Silver    Nanoprisms with Chemically Tailorable Thickness. Advanced Materials,    17, 412-415.-   Schultz, R. K.; Myers, R. R; 1969: The Chemorheology of Poly(vinyl    alcohol)-Borate Gels. Macromolecules, 2, 281-285.-   Xiong, Y. J., A. R. Siekkinen, J. G. Wang, Y. D. Yin, M. J. Kim,    and Y. N. Xia, 2007: Synthesis of silver nanoplates at high yields    by slowing down the polyol reduction of silver nitrate with    polyacrylamide. Journal of Materials Chemistry, 17, 2600-2602.-   Xue, C. M., C. A., 2007: pH-Switchable Silver Nanoprism Growth    Pathways. Angew Chem Int Ed, 46, 2036-2038.

Each of the references listed above is incorporated by reference in itsentirety.

What is claimed is:
 1. A process for making concentrated silvernanoplates that preserve shape post-concentration while increasingoptical density, the process comprising: adding a stabilizing agent to apre-concentrated solution, wherein the pre-concentrated solutioncomprises silver nanoplates, wherein each of the silver nanoplates has aplate shape, wherein the pre-concentrated solution has a peak opticaldensity at a first wavelength; wherein the stabilizing agent comprises apolymer derivatized with sulfonate and a molecule that comprises anamine or thiol chemical group; and increasing a concentration of thesilver nanoplates in the pre-concentrated solution to generate aconcentrated solution, wherein the concentrated solution has a peakoptical density at a second wavelength, wherein the first wavelength issubstantially the same as the second wavelength, wherein the peakoptical density of the concentrated solution is greater than the peakoptical density of the pre-concentrated solution, and wherein at least aportion of the silver nanoplates in the pre-concentrated solution retainthe plate shape in the concentrated solution.
 2. The process of claim 1,wherein the amine chemical group comprises at least one of the groupconsisting of: an aminopropyltriethoxysilane (APTES) and an aminemoiety.
 3. The process of claim 1, wherein the thiol chemical groupcomprises at least one of the group consisting of: a lipoic acid, amercaptohexadecanoic acid, a mercaptoundecanoic acid, and adihydrolipoic acid.
 4. The process of claim 1, wherein the peak opticaldensity of the concentrated solution is at least ten times higher thanthe peak optical density of the pre-concentrated solution, wherein thepeak optical density of the concentrated solution is at least 100 cm⁻¹,wherein the second wavelength of the concentrated solution is in a rangebetween 300 nm and 1500 nm, and wherein at least one optical property ofthe concentrated solution is substantially the same as thepre-concentrated solution in that the peak optical density of thepre-concentrated solution and the peak optical density of theconcentrated solution occurs at substantially the same wavelength, andwherein the portion of the silver nanoplates that retain the plate shapeis greater than 90% in the concentrated solution.
 5. The process ofclaim 1, wherein the silver nanoplates are prepared via a seed mediatedgrowth mechanism, wherein the seed mediated growth mechanism comprises:combining citrate, polystyrene sodium sulfonate (PSSS), and sodiumborohydride in a first solution, adding silver nitrate to the firstsolution to form a seed solution, adding a portion of the seed solutionto a second solution, wherein the second solution comprises ascorbicacid, and adding silver nitrate to the second solution to form thepre-concentrated solution.
 6. The process of claim 1, wherein increasingthe concentration is performed using a filter membrane with pores with amolecular weight cutoff in a range between 10 kDa and 0.05 micron,wherein the peak optical density of the concentrated solution is atleast ten times higher than the peak optical density of thepre-concentrated solution, wherein the peak optical density of theconcentrated solution is at least 100 cm⁻¹.
 7. The process of claim 1,further comprising coating the silver nanoplates with silica, whereincoating the silver nanoplates with silica comprises: adding ethanol tothe pre-concentrated solution, adding a base to the pre-concentratedsolution, and adding a silane to the pre-concentrated solution.
 8. Theprocess of claim 1, wherein the polymer derivatized with sulfonatecomprises polystyrene sodium sulfonate.
 9. The process of claim 1,further comprising forming a metal oxide shell on the surface of thesilver nanoplate.
 10. The process of claim 9, wherein the metal oxideshell is any of the group consisting of: a silica shell and a titaniumdioxide shell, wherein the metal oxide shell has a thickness in a rangebetween 1 nm to 100 nm.
 11. The process of claim 1, wherein the secondwavelength is within 10% of the first wavelength.
 12. The process ofclaim 1, wherein the portion of the concentrated silver nanoplates thatretain the plate shape after increasing the concentration is greaterthan 80%.
 13. The process of claim 1, wherein the pre-concentratedsolution is centrifuged.
 14. The process of claim 1, where thepre-concentrated solution is incubated with a substrate, wherein thesubstrate comprises a fiber.
 15. A composition comprising: a pluralityof silver nanoplates in a solution comprising an optical density,wherein the silver nanoplates comprise a coating on a surface of thesilver nanoplates, wherein the optical density is greater than 100 cm⁻¹,and wherein the coating comprises polystyrene sodium sulfonate and atleast one agent selected from the group consisting of: anamine-containing molecule and a thiol-containing molecule, wherein thecoating further comprises a metal oxide shell, wherein the metal oxideshell is any of the group consisting of: a silica shell and a titaniumdioxide shell, wherein the metal oxide shell has a thickness in a rangebetween 1 nm to 100 nm.
 16. The composition of claim 15, wherein thecoating comprises said amine-containing molecule, wherein theamine-containing molecule comprises at least one of the group consistingof: an aminopropyltriethoxysilane (APTES) and an amine moiety.
 17. Thecomposition of claim 15, wherein the coating comprises saidthiol-containing molecule, wherein the thiol-containing moleculecomprises at least one of the group consisting of: a lipoic acid, amercaptohexadecanoic acid, a mercaptoundecanoic acid, and adihydrolipoic acid.
 18. The composition of claim 15, wherein the metaloxide shell is the silica shell.